Some people suffering from pain from cancer and other chronic illnesses turn to marijuana to relieve their suffering, but much of that relief may come from simply believing that weed will help, a new study finds.
In research, the tendency to have positive expectations that a fake pill, procedure, or treatment will help is called the placebo effect.
“The placebo response was 67% of the pain relief associated with real cannabinoids,” said lead author Karin Jensen, an associate professor and research group leader in the pain neuroimaging laboratory at Karolinska Institutet in the Stockholm area.
“Factors such as patients’ expectations of relief likely play a role in the analgesic effects associated with cannabis-based treatments,” Jensen said in an email.
The results of the recent study, published Nov. 28 in the journal JAMA Network Open, mirror those of another large 2021 analysis of the available evidence by the International Association for the Study of Pain. Based on these findings, the association has issued a statement against the use of marijuana for pain.
“There is not enough high-quality clinical evidence of safety and efficacy in humans to allow IASP to endorse the widespread use of cannabis and cannabinoids for pain at this time,” the association said at the time.
For example, a 2020 study found that using marijuana before entering the hospital for a surgical procedure significantly worsened pain during recovery. People who used weed prior also required more anesthesia during surgery, and undergoing anesthesia can be risky for some people, such as older adults or those with chronic illnesses such as diabetes. Marijuana users also required more opioids during recovery.
Another 2020 analysis of six randomized control trials involving nearly 1,500 cancer patients in the UK and Europe found no change in average pain intensity between those using cannabis and those taking dummy pills. In the study, some cannabis users experienced side effects that were sometimes so severe that they dropped out of the study. Reported side effects included dizziness, nausea, vomiting, fatigue, and somnolence.
“I think we set patients up to expect a certain kind of outcome,” says experimental psychologist Harriet de Wit, a professor of psychiatry and behavioral sciences at the University of Chicago who studies the placebo effect.
“Without a doubt, some people will expect to get the active drug, and they will experience some positive results. That’s true with antidepressants; to be where with painkillers,” said de Wit, who was not involved in the new cannabis study.
“It’s an interesting and very real phenomenon,” she added. “It’s certainly not ‘all in your head.’ And yet there are some brain circuits involved in creating those thoughts and those expectations.”
The effect of the sugar pill
The placebo effect was first discovered in the late 18th century. It quickly became the basis of many of the gruesome treatments doctors used at the time, such as bleeding, blisters, and leeches, just to name a few mentioned in a 1990 magazine article.
“The sheer power of the placebo helps explain why physicians remained useful, respected, and highly honored members of society despite the painful, repugnant, unscientific, and often dangerous treatments they prescribed,” wrote author Charmane Eastman, founder and director of the Biological Rhythm Research. Laboratory at Rush University Medical Center in Chicago.
In modern clinical trials, researchers usually give the tested medication to half of the study participants, while a so-called sugar pill goes to a similar group of people. Neither group is supposed to know which pill they received. If it’s a double-blind study, even the researchers do not know which pill the participants took.
But sometimes people can tell if the pill has an effect that can be felt, like a marijuana high. And even if they can’t say it, people have been known to believe that they did indeed get the experimental dose.
In fact, the optimistic attitude generated by a placebo may be powerful enough to dramatically affect study results. For example, the placebo effect can take this into account 50% to 75% of the positive results found in antidepressant drug trials, according to a 2002 study.
Partly to counteract this effect, scientists only consider the results of a study significant if they exceed chance.
The new study examined 20 studies of cannabis use for pain relief in more than 1,450 people between the ages of 33 and 62. All studies were conducted as double-blind, placebo-controlled clinical trials – meaning that even the researchers did not know which study participant received cannabis or a sham treatment.
Researchers found no difference in self-reported pain relief between cannabis use or placebo in the clinical trials: both showed major improvement in pain. There was also no difference between the duration of treatment – 45 days or several months – both showed improvement in pain.
In clinical trials where blinding was most successful – people had no idea what treatment they were receiving – the placebo response was highest. Participants reported that their pain was moderately to significantly less intense after treatment with a placebo compared to before treatment.
A unique part of the study looked at the role of news and social media for the placebo effect in cannabis clinical trials, Jensen said. Researchers found positive media coverage after each of the cannabis clinical trials trials, even if the study results weren’t spectacular, she said.
“The positive and extensive media coverage may shape placebo responses in subsequent clinical trials, but the current study is not appropriate to address this possibility,” the study said.
More research is needed to understand if this shaping of placebo responses is real happens, Jensen said.
“It’s really hard to say where people get their information from about what they expect the drug to do,” de Wit said. “I don’t think you can explain the placebo effect or blame social media. But you could say that they got there with the expectation that this drug would relieve their pain – there is a lot of social media saying that cannabis is good for everything under the sun.”